FDA-Required Studies of Approved Drugs Make a Big Difference for Public Health

By: Peter Stein. M.D.

Drugs are approved by FDA based upon substantial evidence from clinical trials that the medicine will be both effective and safe for use if prescribed according to its labeling. However, there may be issues that need additional evaluation after approval. For example, post-approval studies may be needed to confirm clinical benefit when a drug is approved under accelerated approval provisions. Additionally, post-approval studies can allow for further evaluation of a potential safety issue or better characterize risk factors for a known safety issue. Once a drug is approved, a larger population and wider range of patients will use the drug than were studied before approval. With this larger experience, new potential safety issues may emerge that were not seen in the studies prior to approval, and such issues may require additional evaluation.

FDA’s ability to require post-approval studies, referred to as post-marketing requirements (PMRs), has evolved over time. Prior to 2007, FDA could require post-approval studies for the few drugs approved under the accelerated approval pathway, for the rare drugs approved based solely on animal studies and, in certain cases, for drugs that may be used in pediatric populations. If FDA wanted other types of post-approval studies, it would seek an agreement with the manufacturer, called a post-marketing commitment or PMC. The FDA Amendments Act of 2007 (FDAAA) was a major step forward for drug safety in the United States. It gave FDA authority to require safety-related PMRs when the agency becomes aware of new safety information.

FDA is committed to making sure industry fulfills their PMRs and PMCs and that the post-market studies are transparent to the public. Certain information about PMRs and PMCs is made available to the public in a searchable database on the agency’s website. Additionally, FDA monitors the progress of PMRs and PMCs to ensure they are conducted in a timely manner. Each year, FDA issues a report via a Federal Register (FR) Notice on the status of PMRs and PMCs. Our most recent FR report shows that, overall, the majority of PMRs and PMCs are progressing toward completion according to the original agreed-upon schedule (85 percent of PMRs and 77 percent of PMCs).

FDA also informs Congress on the status of a subset of PMRs and PMCs, referred to as the “backlog.” FDAAA required FDA to review the PMRs and PMCs that were in place (open) at the time the Act passed in 2007, to determine which ones needed to be revised or eliminated, and to establish completion dates for these PMRs and PMCs. FDAAA also required that FDA report annually to Congress on the progress being made on the backlog. The 9th Annual Report to Congress, which covered fiscal year (FY) 2016, showed that the number of the number of open PMRs and PMCs in the backlog has markedly decreased from 1,636 to 143.

Many factors influence the timely conduct of a study including low use of a product or changes in the standard of care which can reduce the number of patients that can be studied. FDA assesses the justification for any delays and if the justification is appropriate monitors adherence to a revised timetable. The agency can also take enforcement actions if a post-marketing requirement is not met or, depending on the violation, may give a manufacturer the opportunity to voluntarily take prompt, corrective action.

It’s important to note that in the years after a drug’s approval, a great deal more information about the drug, and about the disease it treats, often becomes available. FDA carefully reviews this emerging scientific information—and may conclude that the original post-approval study needs to be revised, with a new schedule for completion, or may be “released,” (no longer required or committed to) if FDA concludes that the new information indicates that the study is no longer needed.

But the important thing for the public to know is that most post-approval studies are on track. When studies are delayed, FDA works with manufacturers to identify the reasons for the delays and ensures that the studies are completed in a timely way. These post-approval studies are vital to enhancing patient safety and public health. The results from completed studies provide additional information that can lead to safety labeling changes, support expanded use of a drug, or alleviate concerns about a potential drug risk. FDA will continue to work to ensure PMRs and PMCs are conducted as promptly as possible.

Peter Stein, M.D., is Deputy Director, Office of New Drugs, at FDA’s Center for Drug Evaluation and Research